LAUROGUADINE is a bactericide, topical antiseptic.

Zaprinast is (M&B 22,948; 2-o-propoxy-phenyl-8-azapurin-6-one) is a selective inhibitor of cyclic GMP (cGMP)-dependent phosphodiesterases, with vasodilation activity in a variety of species and tissues. The potency of zaprinast as a vasorelaxant varies with the species, the tissue, and the presence and absence of endothelium. Zaprinast apparently loses all or most of its vasorelaxant capacity when arteries have been denuded of the endothelial cell layer. Alternatively, the vasorelaxant effects of zaprinast can be attenuated using methylene blue, an inhibitor of soluble guanylate cyclase and hemoglobin inhibitor of nitric oxide synthesis. Therefore, zaprinast-induced relaxations appear to be endothelium-dependent. In human platelets zaprinast, at a dose of 10 mkM, caused a modest (20%) inhibition of aggregation as well as a small increase in cGMP content. In anesthetized rats, zaprinast dose-dependently lowered mean arterial blood pressure (MAP), an effect that correlated well with increased levels of plasma cGMP. Zaprinast decreased mean arterial pressure, the reduction being inversely related to zaprinast concentration. Zaprinast had no effect on heart rate, but increased cardiac output, urinary output, urinary sodium excretion, as well as renal blood flow. Oral administration of zaprinast to spontaneously hypertensive rats at a dose of 200 mg/kg/day normalized blood pressure. In normotensive rats, however, no changes in blood pressure were observed with the same treatment. In an initial placebo-controlled, double-blind crossover trial, 10 mg of zaprinast was effective in reducing exercise-, but not histamine-induced bronchoconstriction in adult asthmatics. However, in a similar study with asthmatic children, zaprinast was ineffective in preventing exercise-induced bronchoconstriction. Since then the clinical development of zaprinast has been discontinued.

Enilospirone (CERM-3726) is essentially a central stimulant. At low doses (100 mg) it may improve performance and at higher doses it may lead to disturbance of sleep continuity. These effects may not involve DA mechanisms, though changes such as those in REM sleep with chronic ingestion could involve the noradrenergic pathway. The property of the drug, even at low doses, to oppose the deterioration in performance associated with tests of prolonged duration is likely to be due to a mild alerting effect.

Merimepodib has immunosuppressive activity. It targets hepatitis C indirectly through the inhibition of inositol monophosphate dehydrogenase, which exerts an acute antiproliferative effect on lymphocyte proliferation due to their almost exclusive dependence on the de novo pathway for synthesis of guanosine. Phase II clinical trial study of merimepodib for the treatment of HCV infection and psoriasis were completed. The poor pharmacokinetic-pharmacodynamic results have resulted in discontinuation of clinical trials.

Metamelfalan is an antineoplastic agent. Metamelfalan is the meta form of the levo isomer melphalan. Metamelfalan causes crosslinking of DNA, thereby preventing DNA replication and eventually cellular proliferation.

Ispinesib (SB-715992) is a potent, specific and reversible inhibitor of kinesin spindle protein (KSP). KSP, also known as HsEg5, is a kinesin that plays an essential role in the formation of a bipolar mitotic spindle and is required for cell cycle progression through mitosis. Ispinesib is the highly specific small-molecule inhibitor of KSP tested for the treatment of human disease. It causes mitotic arrest and growth inhibition in several human tumor cell lines and is currently being tested in multiple phase II clinical trials for treatment of the breast cancer and renal cell cancer.

FLUBANILATE is a CNS stimulant.

Cefoxazole is a semi-synthetic, first-generation cephalosporin with bactericidal activity against penicillin-resistant strains of S. aureus and used in the treatment of bovine mastitis.

MK-0686 is a bradykinin B1 receptor antagonist patented by American multinational pharmaceutical company Merck & Co for the treatment of neuropathic pain and inflammation. MK-0686 demonstrates significantly reduced susceptibility to human P-gp mediated efflux and shows good potential for human CNS penetration based on brain levels in CF-1 mice and monkeys. Additionally, MK-0686 also exhibited good CNS bradykinin B1 receptor occupancy in the transgenic rat expressing the human B1 receptor and showed oral efficacy in reducing CFA-induced hyperalgesia in a humanized mouse. Unfortunately, in phase II clinical trials MK-0686 failed to demonstrate efficacy in phase II clinical trials.

Doxpicomine is the hydrochloride salt of l-3[(dimethylamino)-(m-dioxan-5-yl)methyl]pyridine, a derivative of substituted 1,3 dioxanes. Its analgesic effect appears to be mediated centrally through opiate-like receptors. Preclinical animal studies revealed analgesic activity and duration of action of the same order as that of meperidine and codeine when administered subcutaneously and of codeine but of shorter duration when administered orally. The analgesic effects were reversed by naloxone. The drug did not reduce or antagonize the analgesic effect of morphine. Drowsiness is an expected response to effective analgesics. It was the foremost side effect observed but was of short duration and minimal intensity and did not interfere with the postoperative regimen of coughing, deep breathing, and early ambulation. Nausea and vomiting were not reported after doxpicomine.